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WO2008015950A1 - Inhibiteur d'acat - Google Patents

Inhibiteur d'acat Download PDF

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Publication number
WO2008015950A1
WO2008015950A1 PCT/JP2007/064634 JP2007064634W WO2008015950A1 WO 2008015950 A1 WO2008015950 A1 WO 2008015950A1 JP 2007064634 W JP2007064634 W JP 2007064634W WO 2008015950 A1 WO2008015950 A1 WO 2008015950A1
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WO
WIPO (PCT)
Prior art keywords
present
food
active ingredient
inhibitor
acat
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2007/064634
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English (en)
Japanese (ja)
Inventor
Tatsuji Enoki
Fuyuko Takashima
Hiromu Ohnogi
Ikunoshin Kato
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Takara Bio Inc
Original Assignee
Takara Bio Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Takara Bio Inc filed Critical Takara Bio Inc
Publication of WO2008015950A1 publication Critical patent/WO2008015950A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention relates to a component derived from a natural product having an action of inhibiting an acyl-CoA cholesterol acyltransferase and useful for the treatment or prevention of arteriosclerosis, hyperlipidemia and the like.
  • the fatty streak eventually becomes a fibrous hard spot and protrudes into the blood vessel wall, and as the lesion progresses further, calcification and thrombus attachment accompany the narrowing of the blood vessel cavity, and the hard spot breaks down to cause thrombotic occlusion.
  • tablets are easy to break! /
  • hard spots are rich in lipid components such as cholesterol esters! /. Therefore, inhibiting the activity of acyl-CoA cholesterol-acyltransferase leads to stabilization and regression of arteriosclerotic lesions, leading to the onset and recurrence of acute coronary syndromes based on arteriosclerosis and hyperlipidemia. Be expected.
  • Inhibition of the acyl CoA cholesterol facilyltransferase activity reduces the synthesis of cholesteryl ester that constitutes VLDL in the liver, resulting in a decrease in VLDL synthesis, and inhibition of cholesterol ester binding in the small intestine. Is known to decrease, blood cholesterol and blood neutral fat can be expected to decrease.
  • the button bow is a perennial belonging to the genus Waraboufu, which has the scientific name Peucedanum japonicum. Put a lot of flowers. Its physiological activity is said to be effective in cold, fatigue recovery, and nourishing tonic in its origin, Okisumari, and has been useful for a long time.
  • button bow fu has a cancer suppressive effect (eg, Non-patent Document 1), a disaccharide-degrading enzyme inhibitory action (eg, Patent Document 1), an antioxidant action (eg, Patent Document 2, Non-patent Document 2) It is also known that there are cell activation effects (for example, Patent Document 2) and melanin production suppression effects (for example, Patent Document 2).
  • Non-Patent Document 3 As a characteristic chemical component contained in button bow fu, a plurality of types of coumarin derivatives are known, and their tumor promoter suppression action and the like have been studied (for example, Non-Patent Document 3).
  • Patent Document 1 Japanese Patent Laid-Open No. 2003-26694
  • Patent Document 2 JP 2004-26697 A
  • Non-patent literature 1 T. Morioka and 8 others, Cancer Letters, 2004, Vol. 205, pl 33-141
  • Non-Patent Document 2 Hisamoto et al., J. Agric. Food Chem., 2004, Vol. 5 2, p445 -450
  • Non-Patent Document 3 Fan ⁇ 5 others, Journal of Japanese Botany, 2000, Vol. 7 5, No. 4, p257-261
  • the first invention of the present invention consists of 3'-acetoxy 4'-tigroinoloxy 3 ', 4' dinoid roseserine, its derivatives and pharmaceutically acceptable salts thereof.
  • the present invention relates to an acyl CoA cholesterol acyltransferase inhibitor characterized by containing at least one selected from the group as an active ingredient.
  • a second invention of the present invention relates to a pharmaceutical comprising the acyl CoA cholesterol acyltransferase inhibitor of the first invention of the present invention.
  • a third invention of the present invention relates to a food or beverage comprising the acyl CoA cholesterol acyltransferase inhibitor of the first invention of the present invention.
  • the present invention relates to a pharmaceutical, food or feed that uses a substance having an inhibitory action on an Asinole CoA cholesterol acyltransferase suitable as a food material or a pharmaceutical material that can be safely and easily ingested.
  • acyl CoA cholesterol transferase inhibitor containing at least one selected from the above as an active ingredient, and a pharmaceutical, food or feed containing the inhibitor.
  • the inhibitor, medicine, food or feed is useful for hyperlipidemia, arteriosclerosis, and diseases caused by them, and among them, the food of the present invention has an inhibitory action on acyl-CoA cholesterol acyltransferase. It is useful as a functional food useful for maintaining homeostasis.
  • Acyl CoA cholesterol acyltransferase (also referred to as Facil CoA: cholesterol O-acyltransferase; hereinafter sometimes abbreviated as ACAT) transfers long chain fatty acids from isacyl CoA to cholesterol, It is an enzyme that catalyzes the synthesis of cholesterol esters.
  • ACAT inhibitory action can be easily measured using an assay system as described in Example 1 described later. That is, by mixing a test substance and an enzyme source containing ACAT and evaluating the transfer of the Oleoyl group from radiolabeled Oleoyl-CoA to cholesterol, the ACAT inhibitory effect can be easily measured.
  • a structural formula (hereinafter, sometimes referred to as a compound of the present invention) is shown.
  • This compound is a substance contained in Peucedanum praeruptorum and was first demonstrated to have an ACAT inhibitory action in the present invention. That is, as the active ingredient in the present invention, 3′-acetoxy-4′-tigloyloxy 3 ′, 4 ′ dinoid roseserine, its derivatives and / or pharmaceutically acceptable salts thereof (hereinafter, all of these Which may be referred to as the active ingredients of the invention).
  • the method for producing the compound of the present invention is not particularly limited, but button boo cucumber (Peucedanum praeruptorum) can be used as a raw material.
  • button boo cucumber Pureucedanum praeruptorum
  • various methods can be used from button boufu ethanol extract.
  • button bow when using button bow as a raw material, there is no particular limitation.
  • the ability to use fruits, seeds, seed coats, flowers, leaves, stems, roots, rhizomes and / or whole plants as they are. / Or stems can be used.
  • the compound of the present invention when synthesized, it can also be obtained by combining known methods.
  • 3'-acetoxy 4'-tigroyloxy 3 ', 4'-dihydroserine is any isomer such as any optical isomer, ketoeenol tautomer, geometric isomer, etc. Even so, as long as it has an ACAT inhibitory action, it can be used in the present invention with a force S.
  • substituents are bonded to the skeleton of 3'-acetoxy-4 'tiglyloyloxy-3', 4'-dino or idrothelin as described above to exhibit a desired effect.
  • substituents include aliphatic groups (straight chain aliphatic groups such as methyl, ethyl, and n-propyl groups, and branched aliphatic groups such as isopropyl, isobutyl, prenyl, and geranyl groups).
  • Aromatic group (phenyl group, naphthyl group, biphenyl group, pyrrolyl group, indolyl group, etc.), aromatic aliphatic group (benzyl group, phenethyl group, etc.), hydroxyl group, carboxyl group, sulfate group, phosphate group, thiol Groups, amino groups, nitro groups, alkoxy groups (such as methoxy groups), acyloxy groups (such as acetyl groups), and halogens (such as chlorine, bromine and fluorine).
  • a substance obtained by metabolizing the compound of the present invention to a mammal is also included in the derivative of the present invention.
  • a pharmaceutically acceptable salt is preferable.
  • the salt used include alkali metal salts, alkaline earth metal salts, and salts with organic bases.
  • the pharmaceutically acceptable salt used in the present invention means a salt of a compound that is substantially non-toxic to living organisms and has an ACAT inhibitory action.
  • Examples of the salt include sodium, potassium, calcium, magnesium, ammonium, or protonated benzathine (N, N, benzylene ethylenediamine), choline, ethanolamine, diethanolamine, Examples thereof include salts of ethylenediamine, megramin (N-methyldulamine), venetamine (N-benzylphenethylamine), piperazine or tromethamine (2-amino-2-hydroxymethyl-1,3-propanediol).
  • Derivatives of the compounds of the present invention can be prepared by methods known in the art.
  • a salt of the compound or derivative of the present invention can be easily prepared by a person skilled in the art by any method known in the art.
  • the active ingredient of the present invention is a compound contained in button bow fowl that has been edible since ancient times, and a synthetic compound having an ACAT inhibitory action known so far (for example, FR179254 described later). As will be described later, there is no particular toxicity, and there is no risk of side effects. Therefore, it is possible to safely and appropriately treat or prevent diseases. Therefore, an ACAT inhibitor comprising the active ingredient (hereinafter sometimes referred to as the ACAT inhibitor of the present invention) is effective in the treatment or prevention of a disease that requires an ACAT inhibitory action, and is described below as a pharmaceutical or food product. Alternatively, it is useful as a feed material.
  • the ACAT inhibitor of the present invention is also used for screening drugs for diseases that require ACAT inhibitory action for treatment or prevention, such as arteriosclerosis and hyperlipidemia, and diseases caused by these factors. Useful. Furthermore, the ACAT inhibitor is useful for studying the mechanism of cholesterol ester production and the mechanism of the development of the above-mentioned diseases such as hyperlipidemia and arteriosclerosis.
  • the ACAT inhibitor of the present invention is not particularly limited as long as it contains the above-mentioned active ingredient of the present invention.
  • the active ingredient of the present invention itself, or a composition containing the active ingredient of the present invention. It may be a thing. That is, the content of the active ingredient in the ACAT inhibitor is determined in consideration of the intended use of the ACAT inhibitor. The amount is not particularly limited as long as the expression of the fruit can be obtained. The content of the active ingredient in the ACAT inhibitor of the present invention is usually about !! to 100% by weight. Further, the amount of the ACAT inhibitor used is not particularly limited as long as the desired effect of the present invention can be obtained.
  • the administration method is not particularly limited, and may be appropriately set in the same manner as the medicine described below.
  • the form of use is not particularly limited, and it can be produced in an appropriate form according to the intended use.
  • the present invention also provides a medicament containing the ACAT inhibitor of the present invention (hereinafter referred to as "medicament of the present invention S").
  • the medicament of the present invention is useful for diseases requiring ACAT inhibitory action for treatment or prevention, and the diseases are not particularly limited.
  • hyperlipidemia hypercholesterolemia, hypertriglyceridemia, Metabolic syndrome, multiple risk factor syndrome, arteriosclerosis, ischemic heart disease, acute myocardial infarction, unstable angina, sudden ischemic death, cerebrovascular disorder, chronic obstructive arteriosclerosis, myocardial infarction, angina , Cerebral infarction, subarachnoid hemorrhage, obesity or diseases caused by these (for example, O 'Rourke et al., J. Biol. Chem., 2002, 277 (45), 42557-42562, (See Ohishi et al., Biol. Pharm. Bull., 2003, 26 (8), 1125-1128, and Ohishi et al., Chem. Pharm. Bull., 2001, 49 (7), 830-839).
  • Examples of the medicament of the present invention include those prepared by combining the above-mentioned effective component used as the ACAT inhibitor according to the present invention with a known pharmaceutical carrier. Moreover, as the medicament of the present invention, the active ingredient of the present invention can be blended with other ingredients that can be used for the same use as the active ingredient as described above.
  • the production of the medicament of the present invention is usually carried out by blending the above active ingredient with a pharmaceutically acceptable liquid or solid carrier, and if necessary, a solvent, a dispersant, an emulsifier, a buffer, Agents, excipients, binders, disintegrants, lubricants, etc. are added to form solids such as tablets, granules, powders, powders, capsules, etc., and usually liquids such as liquids, suspensions, and emulsions. be able to.
  • dry products that can be made liquid by adding an appropriate carrier before use, and other externally used IJs are also included.
  • the pharmaceutical carrier can be selected depending on the administration form and formulation of the pharmaceutical.
  • an oral preparation composed of a solid composition it can be a tablet, pill, capsule, powder, fine granule, condyle granule, etc., for example, starch, lactose, sucrose, mannitol, carboxymethy Pharmaceutical carriers such as cellulose, corn starch and inorganic salts are used.
  • binders, disintegrants, surfactants, lubricants, fluidity promoters, flavoring agents, coloring agents, fragrances and the like can be further added.
  • a sugar coating such as sucrose, gelatin or hydroxypropylcellulose, or a film of a gastric or enteric substance, if desired.
  • an oral preparation comprising a liquid composition
  • it can be a pharmaceutically acceptable emulsion, solution, suspension, syrup, etc.
  • purified water, ethanol or the like is used as a carrier.
  • adjuvants such as wetting agents and suspending agents, sweetening agents, flavoring agents, preservatives and the like may be added.
  • a parenteral preparation distilled water for injection, physiological saline, aqueous glucose solution, vegetable oil for injection, sesame oil, peanut oil, soybean oil according to a conventional method, using the above active ingredient of the present invention as a diluent. It can be prepared by dissolving or suspending in corn oil, propylene glycol, polyethylene glycol, etc., and adding bactericides, stabilizers, tonicity agents, soothing agents, etc. as necessary.
  • a solid composition can be produced and used by dissolving in sterile water or a sterilized solvent for injection before use.
  • the external preparation includes solid, semi-solid or liquid preparations for transdermal administration or transmucosal (intraoral or intranasal) administration. Also included are suppositories and the like. For example, emulsions such as emulsions and lotions, liquid preparations such as external tinctures, liquids for transmucosal administration, ointments such as oily ointments and hydrophilic ointments, transdermal such as films, tapes, and poultices It may be a patch for administration or transmucosal administration.
  • the medicaments in the various preparation forms as described above can be appropriately produced by conventional methods using known pharmaceutical carriers and the like.
  • the content of the active ingredient in force and medicinal medicine is particularly limited as long as the active ingredient can be administered within the dosage range described below, taking into consideration its administration form, administration method and the like. It is not something.
  • the content of the active ingredient in the medicament of the present invention is usually about 1 to 100% by weight.
  • the medicament of the present invention is administered by an appropriate administration method according to the preparation form.
  • the administration method is not particularly limited, and for example, it can be administered by internal use, external use or injection.
  • the pharmaceutical agent of the present invention when administered by injection, it can be administered, for example, intravenously, intramuscularly, subcutaneously, intradermally, and when administered externally, for example, as an external preparation such as a suppository, its suitable administration It can be administered by any method.
  • the dosage of the medicament of the present invention is appropriately set according to the formulation form, administration method, purpose of use, and age, weight, and symptoms of the patient to whom the medicament is administered and is not constant.
  • the dosage of the active ingredient contained in the preparation is preferably 0.1 ⁇ g to 5 g / kg body weight, more preferably 1 ⁇ g to 2 g / kg body weight, more preferably 10 per day for an adult. ⁇ g ⁇ lg / kg body weight.
  • Administration may be carried out once or within several days within a desired dose range.
  • the administration period is also arbitrary.
  • the medicament of the present invention can be orally administered as it is orally added to any food.
  • a method for treating a disease using the medicament comprises treating the above-mentioned medicament containing the active ingredient of the present invention with hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, multiple risk factor syndrome, arteriosclerosis, Bloody heart disease, acute myocardial infarction, unstable angina, ischemic sudden death, cerebrovascular disorder, chronic obstructive arteriosclerosis, myocardial infarction, angina, cerebral infarction, subarachnoid hemorrhage, obesity or It is characterized by administration to patients with diseases that occur as causative factors.
  • the conditions for administration of the drug can be implemented in accordance with the aforementioned disclosure of drug administration.
  • 3′-acetoxy 4 'tigloroxy-3', 4'-dino or idroserine for producing the medicament.
  • 3′-Acetoxy-4′-tigroyloxy-3 ′ and 4′-dihydroserine include the aforementioned derivatives and pharmaceutically acceptable salts thereof.
  • the present invention provides an ACAT-inhibiting food or feed comprising the ACAT inhibitor of the present invention (sometimes referred to herein as the food or feed of the present invention). .
  • the food or feed of the present invention has an ACAT inhibitory action of the active ingredient of the present invention.
  • Very useful for prevention That is, the food of the present invention is extremely useful as a functional food (specific health food, etc.) with the purpose of preventing, ameliorating or treating the above-mentioned diseases, and is concerned about blood cholesterol level. It is a very useful food for those who are concerned about neutral fat and those who are concerned about body fat. In the specification of the present application, food includes drinks.
  • containing means containing, adding and / or diluting.
  • containing means that the active ingredient used in the present invention is contained in food or feed
  • addition means that the active ingredient used in the present invention is added to the raw material of food or feed.
  • concentration refers to the addition of food or feed ingredients to the active ingredient used in the present invention.
  • the food of the present invention is not particularly limited.
  • a processed grain product processed flour product, processed starch product, premix processed product, rice cake
  • a processed grain product containing the active ingredient according to the present invention is included.
  • Macaroni breads, bean paste, buckwheat, rice cake, rice noodles, harsame, packaging rice cake etc.
  • Miso, natto, etc. processed meat products (ham, bacon, press ham, sausage, etc.), marine products (frozen surimi, force, maboko, chikuwa, champagne, fried fish cake)
  • the food of the present invention if the active ingredient is contained singly or plurally, contained, added and / or diluted, and the content thereof corresponds to a necessary amount for expressing the ACAT inhibitory action, In particular, powders, tablets, granules, capsules and the like that can be taken orally are also included.
  • the food of the present invention includes foods obtained by mixing the above-mentioned active ingredients of the present invention as they are or appropriately mixed with appropriate emulsifiers and excipients. These foods can be eaten as drinks as they are or mixed with water.
  • the food of the present invention can be mixed with the active ingredient of the present invention and the juice of various plants (vegetables, fruits, etc.) to make a health drink.
  • the active ingredient of the present invention by diluting the active ingredient of the present invention with water, button bouffwa, ij ij old moon Dalefruit, Kiwi, Spinach, Radish, Radish, Chinese cabbage, Cabbage, Salad, Lettuce, Yura, Okra, Pepper, Cucumber, Green beans, Edamada, Endo, Corn, Herb, Summer tangerine, Sweet mandarin It can be mixed with squeezed juice in summer, milk, soy milk, etc. to make a health drink having ACAT inhibitory action.
  • 3'-acetoxyl-4'-tigroyloxy-3 ', 4'-dihydroserine is used as an active ingredient (participating ingredient), and treatment of plants containing the same
  • a product such as an extract or pulverized product of button bow fu, squeeze juice, or the like is used as it is as a food for which the effect of the active ingredient of the present invention is expected, for example, a food for specified health use.
  • the content of the active ingredient in the food of the present invention is not particularly limited, and can be appropriately selected from the viewpoint of its sensory and activity expression.
  • the active ingredient of the present invention in food is preferably 0.001. weight 0/0 or more, more preferably 0.1 0001 ⁇ ; 10 weight 0/0, more preferably 0.00 06-6 wt%.
  • the method for producing the food of the present invention is not particularly limited. For example, blending, cooking, processing, etc. can be produced by a production method that follows general foods, and the obtained food contains the active ingredient according to the present invention having ACAT inhibitory action. If it is done.
  • the food of the present invention contains, for example, the active ingredient of the present invention preferably from 0.1 ag to 1 adult per day.
  • the present invention provides a biological feed having an ACAT inhibitory action, comprising the active ingredient, that is, containing, adding and / or diluting the active ingredient.
  • the present invention also provides a method for raising an organism, which comprises administering the active ingredient to the organism.
  • a biological breeding agent characterized by containing the active ingredient.
  • the organism is not limited, and examples thereof include farm animals and pet animals.
  • Aquaculture animals include domestic animals such as horses, bushes, pigs, hidges, goats, ratadas, llamas, laboratory animals such as mice, rats, guinea pigs, and magpies, poultry such as birds, ducks, turkeys, and birds, fishes, Examples include crustaceans or shellfish.
  • pet animals include Inu and cats.
  • Examples of the feed include a feed for maintaining and / or improving physical condition.
  • the animal breeding agent include an immersion agent, a feed additive, and a beverage additive.
  • the feed of the present invention exerts a therapeutic or preventive effect on diseases requiring ACAT inhibitory action for treatment or prevention in the organism, such as arteriosclerosis and hyperlipidemia, and diseases caused by these factors. Can do.
  • the active ingredient used in the present invention is usually preferably from 0.11 11 g per day to the target organism.
  • the active ingredient can be added and mixed in the raw material of the artificial feed for the target organism or mixed with the powdered raw material of the artificial feed and then further added to and mixed with other raw materials. It can be carried out.
  • the effective The content of the minute in the feed yo Rere force ⁇ column e (or ,, preferably be appropriately set according to the particular limited as those in the nag purposes ⁇ (or 0.00001 weight 0/0 or more, more preferably ⁇ (Between 0.0001 and 10% by weight, more preferably 0.0006 to 6% by weight.
  • the content of the active ingredient of the present invention in the biological breeding agent may be of the same level.
  • the method for producing the feed of the present invention is not particularly limited, and if the formulation is similar to that of a general feed, the active ingredient according to the present invention having an ACAT inhibitory action is included in the prepared feed. It only has to be done.
  • a biological rearing agent can be prepared in the same manner.
  • a feed containing the active ingredient used in the present invention having an ACAT inhibitory action is consumed, or a liquid containing the active ingredient used in the present invention (for example, Or maintaining the physical condition of livestock, laboratory animals, poultry, pet animals, etc., by immersing the target organism in water in which the soaking agent is dissolved in water) Power S can be.
  • a liquid containing the active ingredient used in the present invention for example, Or maintaining the physical condition of livestock, laboratory animals, poultry, pet animals, etc., by immersing the target organism in water in which the soaking agent is dissolved in water
  • Power S can be.
  • the active ingredient used in the present invention is not toxic even if the body is administered in an effective amount for the expression of its action. For example, in the case of oral administration, no deaths are observed even if a single dose of 3'-acetoxy-4 'tigloroxy-3', 4'-dihydroserine is administered to a mouse at lg / kg body weight. In addition, when the active ingredient is orally administered to rats, no mortality is observed even if lg / kg body weight is orally administered once.
  • ACAT enzyme activity of ACAT was measured with some modifications according to the method of Lee et al. (Planta Med., 2004, 70, ⁇ 678-679).
  • a compound was added without adding a dimethyl sulfoxide solution, and as a positive control, a compound containing FR179254 (final concentration 10 M, Merck, 344235) known to have ACAT inhibitory activity was added. Set the minute. Thereafter, 0. 05mCi / mL of Oleoyl Coenzyme A, [oleoyl- 9, 1 0- 3 H] ( Moravec Biochemicals Inc., MT1649) 2 ⁇ L and 0 ⁇ 2 mg / mL of Ole oyl Coenzyme A (ICN 591-20521) 5 L of the mixture was added to each tube, mixed, and then incubated at 37 ° C for 5 minutes.
  • Inhibitory activity (%) ⁇ ([Radioactivity in the control category (cpm)] [Radioactivity in the test sample addition category (cpm)]) / ([Radioactivity in the control category (cpm)] — [10 M of FR179254 calories with category Radioactivity (cpm)]) ⁇ X 100
  • an ACAT inhibitor containing 3'-acetoxy-4'-tigloyloxy-3 ', 4, -dihydric mouth celine, derivatives thereof and / or pharmaceutically acceptable salts thereof, A medicament, food or feed containing it is provided.
  • the medicament is useful as a therapeutic or prophylactic agent for arteriosclerosis, hyperlipidemia, and diseases caused by these factors.
  • the food containing the active ingredient of the present invention is a functional food useful for maintaining homeostasis due to its ACAT inhibitory action.

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Abstract

L'invention concerne un inhibiteur d'acyl-CoA cholestérol acyltransférase comprenant au moins un élément sélectionné parmi le groupe constitué de 3'-acétoxy-4'-tigloyloxy-3'-4'-dihydroseseline, un dérivé de celui-ci et un sel pharmaceutiquement acceptable du composé ou du dérivé en tant qu'ingrédient actif. L'inhibiteur ou un produit pharmaceutique, un aliment ou un aliment pour animaux comprenant l'inhibiteur est efficace dans le traitement de l'hyperlipidémie, de la sclérose artérielle ou d'une maladie associée à ces maladies. En particulier, l'aliment est utile en tant qu'un aliment fonctionnel qui possède une activité inhibitrice sur l'acyl-CoA cholestérol acyltransférase et est efficace pour le maintien de l'homéostasie in vivo.
PCT/JP2007/064634 2006-08-02 2007-07-26 Inhibiteur d'acat Ceased WO2008015950A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2006211310 2006-08-02
JP2006-211310 2006-08-02

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JP2010105976A (ja) * 2008-10-31 2010-05-13 Ss Pharmaceut Co Ltd 中性脂肪蓄積抑制剤
CN102329322A (zh) * 2011-05-31 2012-01-25 苏州派腾生物医药科技有限公司 一种从滨海前胡中提取顺-3＇，4＇-二异戊酰凯林内酯的方法
WO2012111643A1 (fr) * 2011-02-14 2012-08-23 株式会社アミノアップ化学 Promoteur de production d'adiponectine, et composition médicinale, aliment, boisson et aliment pour animaux contenant un promoteur de production d'adiponectine
JP2021107373A (ja) * 2019-12-28 2021-07-29 株式会社 沖縄リサーチセンター 下部尿路症状改善用組成物

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WO2005074906A1 (fr) * 2004-02-06 2005-08-18 Takara Bio Inc. Remede
WO2006082743A1 (fr) * 2005-02-04 2006-08-10 Takara Bio Inc. Agent therapeutique

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WO2005074906A1 (fr) * 2004-02-06 2005-08-18 Takara Bio Inc. Remede
WO2006082743A1 (fr) * 2005-02-04 2006-08-10 Takara Bio Inc. Agent therapeutique

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010105976A (ja) * 2008-10-31 2010-05-13 Ss Pharmaceut Co Ltd 中性脂肪蓄積抑制剤
WO2012111643A1 (fr) * 2011-02-14 2012-08-23 株式会社アミノアップ化学 Promoteur de production d'adiponectine, et composition médicinale, aliment, boisson et aliment pour animaux contenant un promoteur de production d'adiponectine
CN103596581A (zh) * 2011-02-14 2014-02-19 日本阿明诺化学有限公司 脂联素产生促进剂、以及含脂联素产生促进剂的药物组合物、食品与饮料、及饲料
JPWO2012111643A1 (ja) * 2011-02-14 2014-07-07 株式会社アミノアップ化学 アディポネクチン産生促進剤、並びにアディポネクチン産生促進剤を含む医薬組成物、飲食品、及び飼料
CN102329322A (zh) * 2011-05-31 2012-01-25 苏州派腾生物医药科技有限公司 一种从滨海前胡中提取顺-3＇，4＇-二异戊酰凯林内酯的方法
JP2021107373A (ja) * 2019-12-28 2021-07-29 株式会社 沖縄リサーチセンター 下部尿路症状改善用組成物
JP7444375B2 (ja) 2019-12-28 2024-03-06 株式会社 沖縄リサーチセンター 下部尿路症状改善用組成物

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